The chemokine receptor CCR2 and its ligand, monocyte chemoattractant protein-1 represent a critical signaling pathway responsible for the recruitment of monocyte-macrophages. MCP-1 expression is not detectable, or very low in healthy young adult mice, but is found in high concentrations in the eyes of CNV bearing mice with the infiltration of macrophages. Recent studies also demonstrate an association between elevated urinary MCP-1 level and AMD, and the intraocular elevation of MCP-1 in AMD patients with CNV. Mice deficient in CCR2 or MCP-1, have a marked impairment in macrophage influx into sites of inflammation and are protected from inflammatory diseases in a range of animal models –. The reduction in the number of infiltrating macrophages and the following amelioration of CNV formation also occurs in CCR2 KO mice or MCP-1 KO mice. Therefore, the inhibition of macrophages by blockage of the CCR2/MCP-1 signal has emerged as a novel therapeutic target for CNV treatment. Recently, INCB3344, a potent and selective small molecule antagonist of CCR2, was discovered and was demonstrated to have a high ability to compete with MCP-1. INCB3344 rapidly binds both rodent and human CCR2 with a high affinity, inhibits CCR2 binding to MCP-1, and blocks MCP-1- induced signaling and functioning in CCR2-expressing cells. Blocking the CCR2/MCP-1 signal by INCB3344 suppresses macrophage recruitment and attenuates the signs and symptoms of a variety of inflammatory diseases such as peritonitis, delayedtype hypersensitivity, experimental autoimmune encephalomyelitis, atherosclerosis, arthritis and thermal hyperalgesia in animal models. All of these lines of evidence suggest that INCB3344 acts as an effective and ideal tool for treating inflammatory diseases. Given the close relationship between inflammation and neovascularization, we hypothesized that INCB3344 might be of therapeutic value in treating CNV. In this study, we administered INCB3344 to mouse models with different phases of CNV to determine whether this compound has the ability to suppress and regress CNV. We also investigated the possible molecular mechanism of INCB3344 involved in CNV formation. In the present study, we evaluated the therapeutic value of INCB3344, a CCR2 antagonist, on a mouse model of age-related macular degeneration and demonstrated that INCB3344 treatment markedly suppressed new CNV formation and shrank RAD001 established CNVs. To investigate the possible cellular mechanism of INCB3344 suppression of CNV, we evaluated the infiltration of macrophages in the early phase of laser induced CNV and revealed that macrophage infiltration was significantly suppressed by INCB 3344 treatment. In this study, we evaluated the macrophage infiltration on Day 3, the day of peak macrophage response. We delivered INCB3344 to the vitreous cavity immediately after photocoagulation. After photocoagulation, local MCP-1 increases quickly, and recruits monocytes, to laser injury sites, where they become inflammatory macrophages. Acting as a CCR2 antagonist, INCB3344 has displayed a high ability to inhibit monocyte chemotaxis in vitro and suppress macrophage influx in a variety of preclinical animal models of inflammatory diseases. Moreover, recent research reports that topical treatment of a CCR2 antagonist leads to the blocking of CCR2/MCP-1.